Leukemia, Myeloid, Acute Myelodysplastic Syndromes
Conditions
Interventions
investigational material(s)
Generic name etc : Pevonedistat
INN of investigational material : Pevonedistat
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investig
Pevonedistat 25 mg/m^2: Pevonedistat, 25 milligram per square meter (mg/m^2), 60-minute infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in 21-day treatment cycles.
G
Pevonedistat 44 mg/m^2: Pevonedistat, 44 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in 21-day treatment cycles.
Generic name etc : Pevonedist
Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2: Pevonedistat 10 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m^2, on Days 1 to 5, and Days 8 and 9, intravenously
Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2: Pevonedistat 20 mg/m^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m^2, on Days 1 to 5, and Days 8 and 9, intravenously
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. East Asian patients aged 18 years or older (or minimum age of legal consent consistent with local regulations) when written study informed consent is obtained must meet 1 of the following diagnosis criteria for either the Single-Agent Arm or the Combination Arm (additional restrictions apply to the Single Agent Arm): - Are male and female participants with WHO-defined AML, including leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve CR or who have relapsed after prior therapy (R/R) and are not candidates for potentially curative treatment, or - Are male and female participants aged 60 years or older with previously untreated AML who have bone marrow blasts =5%. 2. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 3. Able to undergo bone marrow aspiration and biopsy at Screening.
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia (as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics [t (15:17)] of peripheral blood or bone marrow, or by other accepted analysis) or AML associated with t (9;22) karyotypes or molecular. 2. More than 3 prior lines of therapy (Combination Arm only). 3. Prior therapy with hypomethylating agents (example, azacitidine, decitabine) (Combination Arm only). 4. Is eligible for a hematopoietic stem cell transplant. 5. Is a female participant who is lactating and breastfeeding or who have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug. 6. Had treatment with any investigational products within 14 days before the first dose of any study drug. 7. Has known hypersensitivity to azacitidine or mannitol (Combination Arm only). 8. Has known central nervous system involvement. 9. Had systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of any study drug, except for hydroxyurea.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number of Participants Reporting one or More Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Time Frame: Throughout study from Baseline up to 30 days after the last dose of study drug safety Number of Participants With Dose Limiting Toxicities (DLTs) During Cycle Time Frame: Cycle 1 Day 1 up to end of Cycle 1 (Day 21 for single-agent groups and Day 28 for combination groups) Toxicity will be evaluated according to NCI CTCAE, Version4.03. DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications. safety Number of Participants With Markedly Abnormal Laboratory Values Time Frame: Baseline and up to 30 days after the last dose of study drug pharmacokinetics Cmax: Maximum Observed Plasma Concentration for Pevonedistat Time Frame: Day 1: Pre-infusion and at multiple time points (up to 48 hours) post-infusion pharmacokinetics AUC (0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time tau Over the Dosing Interval for Pevonedistat Time Frame: Day 1: Pre-infusion and at multiple time points (up to 48 hours) post-infusion pharmacokinetics CL: Clearance Time Frame: Days 1 and 5: Day 1: Pre-infusion and at multiple time points (up to 48 hours) post-infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Percentage of Participants With Overall Response Time Frame: Screening until CR or PR, assessed within 6 days before Day 21 for single-agent groups and Day 20 to 28 for combination groups of Cycle 2, 4 and every 3 cycles thereafter up to Day 35 for single-agent groups and Day 39 for combination groups efficacy Percentage of Participants With CR Time Frame: Screening until CR or PR, assessed within 6 days before Day 21 for single-agent groups and Day 20 to 28 for combination groups of Cycle 2, 4 and every 3 cycles thereafter up to Day 35 for single-agent groups and Day 39 for combination groups | — |
Countries
Japan, South Korea, Taiwan
Outcome results
None listed